Nomogram for Predicting Viral Shedding Time of SARS-CoV-2 Delta Variant in Patients with COVID-19: A Retrospective Study

Background The coronavirus disease 2019 (COVID-19) cases continue to rise, and the demand for medical treatment and resources in healthcare systems surges. Assessing the viral shedding time (VST) of patients with COVID-19 can facilitate clinical decision making. Although some studies have been conducted on the factors affecting the VST of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), few prediction models are currently available. Methods This retrospective study included the consecutive patients with COVID-19 admitted to Xi'an Chest Hospital in Shaanxi, China, for treatment between December 19, 2021 and February 5, 2022. The clinical data of the patients were extracted from their electronic medical records. Combining significant factors affecting the VST, a nomogram was developed to predict the VST of the SARS-CoV-2 Delta variant in patients with COVID-19. Results We included 332 patients in this study. The average VST was 21 d. VST was significantly prolonged in patients with severe clinical symptoms, sore throat, old age, long time from onset to diagnosis, and an abnormal white blood cell count. Consequently, we developed a nomogram prediction model using these 5 variables. The concordance index (C-index) of this nomogram was 0.762, and after internal validation using bootstrapping (1000 resamples), the adjusted C-index was 0.762. The area under the nomogram's receiver operator characteristic curve showed good discriminative ability (0.965). The calibration curve showed high consistency. The VST was prolonged in the group with lower model fitting scores according to the Kaplan-Meier curve (χ2=286, log-rank P < 0.001). Conclusions We developed a nomogram for predicting VST based on 5 easily accessible factors. It can effectively estimate the appropriate isolation period, control viral transmission, and optimize clinical strategies.

A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice.

Innate immune cells are critical in antitumor immune surveillance and the development of antitumor adaptive cellular immunity. Trained innate immune cells demonstrate immune memory-like characteristics, producing more vigorous immune responses to secondary homologous or heterologous stimuli. This study aimed to investigate whether inducing trained immunity is beneficial when using a tumor vaccine to promote antitumor adaptive immune responses. A biphasic delivery system was developed with the trained immunity inducer Muramyl Dipeptide (MDP) and specific tumor antigen human papillomavirus (HPV) E7 peptide encapsulated by poly(lactide-co-glycolide)-acid(PLGA) nanoparticles (NPs), and the NPs along with another trained immunity agonist, ß-glucan, were further embedded in a sodium alginate hydrogel. The nanovaccine formulation demonstrated a depot effect for E7 at the injection site and targeted delivery to the lymph nodes and dendritic cells (DCs). The antigen uptake and maturation of DCs were significantly promoted. A trained immunity phenotype, characterized by increased production of IL-1ß, IL-6, and TNF-α, was induced in vitro and in vivo in response to secondary homologous or heterologous stimulation. Furthermore, prior innate immune training enhanced the antigen-specific INF-γ-expressing immune cell response elicited by subsequent stimulation with the nanovaccine. Immunization with the nanovaccine completely inhibited the growth of TC-1 tumors and even abolished established tumors in mice. Mechanistically, the inclusion of ß-glucan and MDP significantly enhanced the responses of tumor-specific effector adaptive immune cells. The results strongly suggest that the controlled release and targeted delivery of an antigen and trained immunity inducers with an NP/hydrogel biphasic system can elicit robust adaptive immunity, which provides a promising tumor vaccination strategy.

Investigating impacts of COVID-19 on urban mobility and emissions.

The COVID-19 pandemic has severely impacted human activities in a way never documented in modern history. The prevention policies and measures have abruptly changed well-established urban mobility patterns. In this context, we exploit different sources of urban mobility data to gain insights into the effects of restrictive policies on the daily mobility and exhaust emissions in pandemic and post-pandemic periods. Manhattan, the most densely populated borough in New York City, is chosen as the study area. We collect data generated by taxis, sharing bikes, and road detectors between 2019 and 2021, and estimate exhaust emissions using the COPERT (Computer Programme to calculate Emissions from Road Transport) model. A comparative analysis is conducted to identify important changes in urban mobility and emission patterns, with a particular focus on the lockdown period in 2020 and its counterparts in 2019 and 2021. The results of the paper fuel the discussion on urban resilience and policy-making in a post pandemic world.

Classic Signaling Pathways in Alveolar Injury and Repair Involved in Sepsis-Induced ALI/ARDS: New Research Progress and Prospect.

Sepsis is a common critical clinical disease with high mortality that can cause approximately 10 million deaths worldwide each year. Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a common clinical complication of sepsis, which occurs primarily as diffuse alveolar injury, hypoxemia, and respiratory distress. The mortality rate of ALI/ARDS is as high as 30%-40%, which greatly endangers human health. Due to the unclear pathogenesis of ALI/ARDS, its treatment is still a worldwide problem. At present, clinical treatment mainly relies on lung-protective ventilation, prone position ventilation, and fluid management. However, there is a lack of effective and specific treatment measures. In recent years, domestic and foreign scholars have committed to basic research on ALI/ARDS, trying to further clarify its pathogenesis and find new targets and methods for the treatment of ALI/ARDS. In this review, we summarize the signaling pathways related to alveolar injury and repair in sepsis-induced ALI/ARDS and their latest research progress. They include the NF-κB, JAK2/STAT3, mitogen-activated protein kinase (MAPK), mTOR, and Notch signaling pathways. Understanding the molecular mechanisms of these signaling pathways in sepsis-induced ALI/ARDS may provide new targets and ideas for the clinical treatment of this disease.

The application of technology to improve cognition in older adults: A review and suggestions for future directions.

The rapidly increasing worldwide population of older adults, along with the increasing prevalence of cognitive impairment and dementia in this population, is a growing health-care problem. As such, advances in technology-based cognitive interventions and games are playing an increasingly key role in preserving and improving older adults' cognitive function, especially during the COVID-19 pandemic when opportunities for face-to-face activities or training are few. In this paper, we summarize from previous studies systematic reviews and meta-analyses on the various types of technology used in cognitive interventions (namely, computerized cognitive training, virtual-reality interventions and robot-assisted interventions) and the empirical evidence on the effects of these technologies on global and specific cognitive functions in healthy and clinical populations of older adults (e.g., older adults with mild cognitive impairment or dementia). We also describe older adults' perceptions, experiences and acceptance of these technologies. Finally, we discuss the limitations, challenges and future avenues of research in this field.

Recombinant VLPs empower RBM peptides showing no immunogenicity in native SARS-COV-2 protein to elicit a robust neutralizing antibody response.

New SARS-COV-2 vaccine strategies are still urgently needed, especially for emerging virus mutations and variants. In this study, we focused on analyzing the antigenicity and vaccine potency of linear peptide epitopes located in receptor binding motif (RBM) of spike (S) protein. Nine 12 to 16-mer overlapping peptides (P1-P9) were synthesized chemically and coupled to carrier protein KLH for the immunization in mice. Four of identified peptides were further engineered to present on the surface of recombinant Hepatitis B core antigen (HBcAg) virus-like particles (VLPs) respectively. Antisera obtained from VLPs -immunized mice demonstrated strong reactivity and affinity to S1 protein or inactivated virus and neutralizing activity against virus infection in vitro. This study indicates that recombinant VLPs empower peptides which display underprivileged antigenicity in native protein to elicit high levels of neutralizing antibody, providing potential epitope candidates and an effective delivery strategy for the development of a multi-epitope vaccine.

The Impact of Age Difference on the Efficacy and Safety of COVID-19 Vaccines: A Systematic Review and Meta-Analysis.

Objective: This meta-analysis compared the efficacy and safety of five kinds of COVID-19 vaccines in different age groups (young adults and older adults), aiming to analyze the difference of adverse events (AEs) rate and virus geometric mean titer (GMT) values between young and older people, in order to find a specific trend, and explore the causes of this trend through meta-analysis. Method: Meta-analysis was used to analyze the five eligible articles. The modified Jadad scoring scale was used to evaluate the quality of eligible literature with a scoring system of 1 to 7. The primary endpoint of the effectiveness index was GMT. The primary endpoints of the safety index were the incidence of local AEs and systemic AEs. Stata 12.0 software was used for meta-analysis. Revman 5.0 software was used to map the risk of publication bias, and Egger's test was used to analyze publication bias. Results: The GMT values of young adults were higher than older adults (SMD = 1.40, 95% CI (0.79, 2.02), P<0.01). There was a higher incidence of local and systemic AEs in young people than in the elderly (OR = 1.10, 95% CI (1.08, 1.12), P<0.01; OR = 1.18, 95% CI (1.14, 1.22), P<0.01). Conclusion: The immune effect of young people after being vaccinated with COVID-19 vaccines was better than that of the elderly, but the safety was worse than that of old people, the most common AEs were fever, rash, and local muscle pain, which were tolerable for young people. As the AEs of the elderly were lower, they can also be vaccinated safely; the reason for the low level of GMT in the elderly was related to Immunosenescence. The vaccine tolerance of people of different ages needs to be studied continuously.

RBD-Modified Bacterial Vesicles Elicited Potential Protective Immunity against SARS-CoV-2.

The disease caused by SARS-CoV-2 infection threatens human health. In this study, we used high-pressure homogenization technology not only to efficiently drive the bacterial membrane to produce artificial vesicles but also to force the fusion protein ClyA-receptor binding domain (RBD) to pass through gaps in the bacterial membrane to increase the contact between ClyA-RBD and the membrane. Therefore, the load of ClyA-RBD on the membrane is substantially increased. Using this technology, we constructed a "ring-like" bacterial biomimetic vesicle (BBV) loaded with polymerized RBD (RBD-BBV). RBD-BBVs injected subcutaneously can accumulate in lymph nodes, promote antigen uptake and processing, and elicit SARS-CoV-2-specific humoral and cellular immune responses in mice. In conclusion, we evaluated the potential of this novel bacterial vesicle as a vaccine delivery system and provided a new idea for the development of SARS-CoV-2 vaccines.

Metagenomic analysis reveals oropharyngeal microbiota alterations in patients with COVID-19.

COVID-19 remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by shotgun metagenomic sequencing analyses of oropharynx swab specimens from 31 COVID-19 patients, 29 influenza B patients, and 28 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in the COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Veillonella and Megasphaera and depletion of Pseudopropionibacterium, Rothia, and Streptococcus. Based on the relative abundance of the oropharyngeal microbiome, we built a microbial classifier to distinguish COVID-19 patients from flu patients and healthy controls with an AUC of 0.889, in which Veillonella was identified as the most prominent biomarker for COVID-19 group. Several members of the genus Veillonella, especially Veillonella parvula which was highly enriched in the oropharynx of our COVID-19 patients, were also overrepresented in the BALF of COVID-19 patients, indicating that the oral cavity acts as a natural reservoir for pathogens to induce co-infections in the lungs of COVID-19 patients. We also found the increased ratios of Klebsiella sp., Acinetobacter sp., and Serratia sp. were correlated with both disease severity and elevated systemic inflammation markers (neutrophil-lymphocyte ratio, NLR), suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the inflammatory response. Moreover, the oropharyngeal microbiome of COVID-19 patients exhibited a significant enrichment in amino acid metabolism and xenobiotic biodegradation and metabolism. In addition, all 26 drug classes of antimicrobial resistance genes were detected in the COVID-19 group, and were significantly enriched in critical cases. In conclusion, we found that oropharyngeal microbiota alterations and functional differences were associated with COVID-19 severity.

Undocumented Migrants Reintroducing COVID-19, Yunnan Province, China.

To limit the spread of severe acute respiratory syndrome coronavirus 2, the government of China has been monitoring infected travelers and minimizing cold-chain contamination. However, other factors might contribute to recurring outbreaks. We analyze the role of undocumented migrants as potential transmitters of severe acute respiratory syndrome coronavirus 2 in China.

Effect of a genetically engineered interferon-alpha versus traditional interferon-alpha in the treatment of moderate-to-severe COVID-19: a randomised clinical trial.

BACKGROUND: There are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. To compare the effectiveness of a novel genetically engineered recombinant super-compound interferon (rSIFN-co) with traditional interferon-alpha added to baseline antiviral agents (lopinavir-ritonavir or umifenovir) for the treatment of moderate-to-severe COVID-19. METHOD: In this multicenter randomized (1:1) trial, patients hospitalized with moderate-to-severe COVID-19 received either rSIFN-co nebulization or interferon-alpha nebulization added to baseline antiviral agents for no more than 28 days. The primary endpoint was the time to clinical improvement. Secondary endpoints included the overall rate of clinical improvement assessed on day 28, the time to radiological improvement and virus nucleic acid negative conversion. RESULTS: A total of 94 patients were included in the safety set (46 patients assigned to rSIFN-co group, 48 to interferon-alpha group). The time to clinical improvement was 11.5 days versus 14.0 days (95% CI 1.10 to 2.81, p = .019); the overall rate of clinical improvement on day 28 was 93.5% versus 77.1% (difference, 16.4%; 95% CI 3% to 30%); the time to radiological improvement was 8.0 days versus 10.0 days (p = .002), the time to virus nucleic acid negative conversion was 7.0 days versus 10.0 days (p = .018) in the rSIFN-co and interferon alpha arms, respectively. Adverse events were balanced with no deaths among groups. CONCLUSIONS AND RELEVANCE: rSIFN-co was associated with a shorter time of clinical improvement than traditional interferon-alpha in the treatment of moderate-to-severe COVID-19 when combined with baseline antiviral agents. rSIFN-co therapy alone or combined with other antiviral therapy is worth to be further studied.Key messagesThere are few effective therapies for coronavirus disease 2019 (COVID-19) upon the outbreak of the pandemic. Interferon alphas, by inducing both innate and adaptive immune responses, have shown clinical efficacy in treating severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus.In this multicenter, head-to-head, randomized, clinical trial which included 94 participants with moderate-to-severe COVID-19, the rSIFN-co plus antiviral agents (lopinavir-ritonavir or umifenovir) was associated with a shorter time of clinical improvement than interferon-alpha plus antiviral agents.

Benevolent Creativity Buffers Anxiety Aroused by Mortality Salience: Terror Management in COVID-19 Pandemic.

With the outbreak of the COVID-19 crisis, the public keeps getting epidemic-related information on the media. News reports on the increasing number of fatalities have exposed individuals to death, which causes negative emotional experiences such as tension, anxiety, and fear. This study aimed to investigate whether creativity could serve as an anxiety-buffer when mortality is salient. Based on previous findings, the present study utilized type of creative task and personal search for meaning as moderators. In Study 1, a 2 (mortality salience: absent, present) × 2 (type of creative task: benevolent, malevolent) between-subject design was utilized, and 168 subjects were randomly assigned to four experimental conditions. In Study 2, 221 subjects were recruited. The experimental procedure was similar to Study 1, except that the priming paradigm of mortality was changed and search for meaning was included as an additional moderating variable. State anxiety was measured as the dependent variable in both studies. Results of Study 1 showed that, while the benevolent creative task could buffer anxiety in the mortality salience condition, the malevolent creative task did not have the same effect. Furthermore, there was a significant interaction between mortality salience, type of creative task, and search for meaning in life on anxiety. In Study 2, the buffering function of benevolent creativity was more intense for participants with a higher level of search for meaning. Together, these findings reveal the influence of different types of creative tasks on individual anxiety levels under death priming conditions and the moderating effect of search for meaning in this relationship. Further, they suggest the need to focus on the role of creativity in terror management.

Sec-Eliminating the SARS-CoV-2 by AlGaN Based High Power Deep Ultraviolet Light Source.

The world-wide spreading of coronavirus disease (COVID-19) has greatly shaken human society, thus effective and fast-speed methods of non-daily-life-disturbance sterilization have become extremely significant. In this work, by fully benefitting from high-quality AlN template (with threading dislocation density as low as ≈6×108 cm-2) as well as outstanding deep ultraviolet (UVC-less than 280 nm) light-emitting diodes (LEDs) structure design and epitaxy optimization, high power UVC LEDs and ultra-high-power sterilization irradiation source are achieved. Moreover, for the first time, a result in which a fast and complete elimination of SARS-CoV-2 (the virus causes COVID-19) within only 1 s is achieved by the nearly whole industry-chain-covered product. These results advance the promising potential in UVC-LED disinfection particularly in the shadow of COVID-19.